Gene expression signature associated with BRAFV600E mutation based on transgenic mouse model (mouse)

BRAFV600E mutation is the most frequent molecular event in papillary thyroid carcinoma. The relation of this genetic alteration with the factors od poor prognosis has been reported as well as its influence on PTC gene signature. However human material disables distinction of cancer causes from its effect. We used our transgenic mouse model of papillary thyroid carcinoma induced by the BRAFV600E mutation to select BRAFV600E-specific gene signature The transgenic mouse model was obtained by the microinjection of the transgene, composed of the human BRAF cDNA with V600E mutation under the control of bovine thyroglobulin, into the ferilized mice egg cells. Three lines were derived and mice after 4-24 months were sacrificed and histopathological evaluation of thyroids was carried out. In order to find BRAFV600E-specific gene signature microarray analysis was performed. The analysis invloved 38 mice thyroid samples: 10 mice papillary thyroid carcinomas, 10 borderline lesions (all being BRAF-positive), 10 apparently asymptomatic thyroids (5 BRAF-positive and 5 BRAF-negative) and 8 benign hyperplastic lesions (4 BRAF-positive and 4 BRAF-negative). Multofactoral analyses were performed in order to define some additional factors that could have impact on the gene expression profile.